Corticosterone suppresses IL-1β-induced mPGE2 expression through regulation of the 11β-HSD1 bioactivity of synovial fibroblasts in vitro

Wei,Bo; Zhu,Zhaobo; Xiang,Min; Song,Lijun; Guo,Weixiong; Lin,Hao; Li,Guangsheng; Zeng,Rong

doi:10.3892/etm.2017.4238

Corticosterone suppresses IL-1β-induced mPGE2 expression through regulation of the 11β-HSD1 bioactivity of synovial fibroblasts in vitro

Authors:
- Bo Wei
- Zhaobo Zhu
- Min Xiang
- Lijun Song
- Weixiong Guo
- Hao Lin
- Guangsheng Li
- Rong Zeng
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Affiliations: Orthopedic Centre, Affiliated Hospital of Guangdong Medical College, Zhanjiang, Guangdong 524001, P.R. China, Reproductive Research Department, Affiliated Hospital of Guangdong Medical College, Zhanjiang, Guangdong 524001, P.R. China
Published online on: March 20, 2017 https://doi.org/10.3892/etm.2017.4238
Pages: 2161-2168
Copyright: © Wei et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The aim of the present study was to investigate the correlation between glucocorticoid activity regulation, prostaglandin E2 (PGE2) synthesis, and synovial inflammation inhibition activity, through microsomal prostaglandin E synthase-1 (mPGES-1) expression regulated by the glucocorticoid pre-receptor regulator, 11β-hydroxysteroid dehydrogenase-1 (11β-HSD1). In the present study, fibroblast-like synovial cells of rats were studied as a cell model. Cells were stimulated with 10 ng/ml interleukin (IL)-1β for 24 h, and were subsequently, within the next 24 h, treated with or without 10-6 mmol/l corticosterone alone or with 100 nmol/l PF915275. At the end of the second 24 h, PGE2 levels in culture supernatants were assayed. Cells were harvested for mRNA evaluation of 11β‑HSD1, mPGES‑1, IL‑1β and tumor necrosis factor (TNF)‑α, and protein detection of 11β‑HSD1 and mPGES‑1 using reverse transcription‑qualitative polymerase chain reaction and western blot analysis, respectively. Corticosterone was demonstrated to suppress the mRNA expression levels of inflammatory factors, such as TNF‑α and PGE2, induced by IL‑1β in vitro. Simultaneously, expression levels of 11β‑HSD1 decreased significantly at the mRNA and protein levels (P<0.05). Cortisol concentration in the medium of the group treated with corticosterone was significantly increased (P<0.05) compared with that of the control group; however, the cortisol concentration was decreased in the medium when the conversion bioactivity of 11β-HSD1 was inhibited by PF915275, while the changes in 11β‑HSD1 and mPGES‑1 mRNA expression levels and PGE2 content were reversed in the medium. These results indicated that a significant positive correlation (P<0.01) may exist between mRNA and protein expression levels. To conclude, 11β‑HSD1 is a key regulator for the synthesis of mPGES‑1 and PGE2 in the inflammatory synovial cells in vitro, suggesting a potential interference target for osteoarthritis.

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